The expression of glucose transporters and mitochondrial division and fusion proteins in rats exposed to hypoxic preconditioning to attenuate propofol neurotoxicity.

Purpose: Evidence has shown that propofol may cause widespread apoptotic neurodegeneration. Hypoxic preconditioning has been demonstrated to provide neuroprotection and brain recovery from both acute and chronic neurodegeneration in several cellular and animal models. However, the mechanism has not been well elucidated. Therefore, the present study was designed to investigate the expression of glucose transporters (GLUT1 and GLUT3) and mitochondrial division and fusion (Drp1 and Mfn2) proteins in rats exposed to hypoxic preconditioning to attenuate propofol neurotoxicity.Methods: Propofol (100 mg/kg) was given to 7-day-old Sprague-Dawley rats; in some rats, hypoxic preconditioning was administered before intraperitoneal propofol injection by subjecting rats to five cycles of 10 min of hypoxia (8% O2) and 10 min of normoxia (21% O2). Then, the rats were allowed to breathe room air for 2 h. Neuronal mitochondrial morphology was observed by transmission electron microscopy. ATP content was detected using an ATP assay kit. The expression levels of GLUT1, GLUT3, pDrp1, Drp1 and Mfn2 were detected by Western blot, and the expression levels of GLUT1 and GLUT3 were further examined by immunohistochemistry.Results: Propofol damaged mitochondria, and decreased ATP content and GLUT3 and pDrp1 protein expression. However, our results suggested that hypoxic preconditioning could attenuate propofol neurotoxicity by reducing mitochondrial damage and increasing ATP content and pDrp1, GLUT1 and GLUT3 protein expression.Conclusion: Hypoxic preconditioning reduced propofol-induced damage in the hippocampus of neonatal rats by attenuating the increase in mitochondrial division and decrease in GLUT3 expression.

Identification of vasospasm biomarkers for cerebral hemorrhage via bio-informatics analysis.

BACKGROUND: The incidence of cerebral hemorrhage has rapidly increased over time, and vascular dysfunction has a significant influence on the pathogenesis and outcome of these patients. This is also the case for vasospasm in cerebral hemorrhage, but there is no method to assess this. We conducted this study to find molecular biomarkers of vasospasm in cerebral hemorrhage patients. METHODS: Raw data of GSE37924 was downloaded from the Gene Expression Omnibus (GEO) database, including 66 samples with cerebral vasospasm and 62 samples without cerebral vasospasm. Differentially expressed genes (DEGs) between samples with cerebral vasospasm and those without cerebral vasospasm were analyzed using the limma package in R software. To determine the functions of DEGs, we conducted functional enrichment analysis of DEGs through the clusterProfiler package in R. The protein-protein interaction (PPI) network of DEGs was constructed through STRING (https://string-db.org/) and generated via Cytoscape software. To understand the correlation between DEGs and immune-related genes, immune-related cerebral vasospasm genes were obtained via intersecting immune-related genes and cerebral vasospasm DEGs. We also compared the infiltration of 28 immune cells between cases with cerebral vasospasm and those without cerebral vasospasm. Finally, we constructed a model to perform the validation experiments. RESULTS: Of the DEGs, there were 24 upregulated and 21 downregulated genes in the vasospasm samples compared to the no-vasospasm samples. Functional enrichment analysis showed that these genes play key roles in several biological processes and signaling pathways such as the bone morphogenetic protein (BMP) signaling pathway, cellular response to BMP stimulus, natural killer cell chemotaxis, negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway, MHC protein complex binding, and receptor ligand activity, among others. CCL4, HLA-DQA1, IGF2, NTS, and so on were the significant immune-related genes. Furthermore, the immune cell infiltration results showed that there were differences between patients with vasospasm and those without vasospasm. Finally, we found that CCL4 had significantly higher expression in patients with vasospasm than those without vasospasm. CONCLUSIONS: CCL4 is an important regulator of vascular dysfunction in cerebral hemorrhage.

Exogenous morphine inhibits human gastric cancer MGC- 803 cell growth by cell cycle arrest and apoptosis induction.

Morphine is not only an analgesic treating pain for patients with cancer but also a potential anticancer drug inhibiting tumor growth and proliferation. To gain better insight into the involvement of morphine in the biological characteristics of gastric cancer, we investigated effects on progression of gastric carcinoma cells and the expression of some apoptosis-related genes including caspase-9, caspase-3, survivin and NF-κB using the MGC-803 human gastric cancer cell line. The viability of cells was assessed by MTT assay, proliferation by colony formation assay, cell cycle progression and apoptosis by flow cytometry and ultrastructural alteration by transmission electron microscopy. The influences of morphine on caspase-9, caspase-3, survivin and NF-κB were evaluated by semi-quantitative RT-PCR and Western blot. Our data showed that morphine could significantly inhibit cell growth and proliferation and cause cell cycle arrest in the G2/M phase. MGC-803 cells which were incubated with morphine also had a higher apoptotic rate than control cells. Morphine also led to morphological changes of gastric cancer cells. The mechanism of morphine inhibiting gastric cancer progression in vitro might be associated with activation of caspase-9 and caspase-3 and inhibition of survivin and NF-κB.